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Journal of Psychiatric and Mental Health Nursing, 2001, 8, 191–196 © 2001 Blackwell Science Ltd 191 The use of outcome measures to evaluate the efficacy and tolerability of antipsychotic medication: a comparison of Thorn graduate and CPN practice R. GRAY 1 rn bs c( h ons), T. WYKES 2 p hd , A.-M. PARR 3 , E. HAILS 4 rn ms c enb a48 pgce & K. GOURNAY 5 cbe mphil p hd cpsychol afbpss frcn rn 1 MRC Fellow, Health Services Research Department, Institute of Psychiatry, 2 Professor of Rehabilitation and Clinical Psychology, Department of Psychology, 3 Research Worker, 4 Thorn-Tutor, and 5 Professor of Psychiatric Nursing, Health Services Research Department, Institute of Psychiatry, De Crespigny Park, London, UK GRAY R., WYKEST., PARR A.-M., HAILS E. & GOURNAY K. (2001) Journal of Psychiatric and Mental Health Nursing 8, 191–196 The use of outcome measures to evaluate the efficacy and tolerability of antipsychotic medication: a comparison of Thorn graduate and CPN practice Assessing the tolerability and efficacy of treatment with antipsychotic medication is a vital part of mental health care. Research has suggested that many side-effects go undetected by clinicians and there is a need to use standardized assessment tools to ensure that treatments are comprehensively evaluated. The training of Community Psychiatric Nurses (CPNs), who provide much of patients’ care, should focus on enhancing skills in using such assess- ments. This study aimed to examine differences in the use of standardized assessments of antipsychotic side-effects and psychopathology by CPNs and Thorn graduates who had received additional training in delivering psychosocial interventions. A questionnaire was sent to 240 Thorn graduates and CPNs practising in England, with an overall adjusted response rate of 54%. Thorn graduates reported using significantly more standardized assessments of side-effects and psychopathology than CPNs. A trend in both groups towards the use of measures that relied on patient self-report of side-effects was observed. This study identified important deficiencies in current CPN practice. A programme of targeted training may be a more realistic and efficient method of enhancing medication management practices in large numbers of CPNs compared to the more expensive and time- consuming Thorn programme. Keywords: antipsychotic, CPN, survey, Thorn, training Accepted for publication: 12 October 2000 Correspondence: R. Gray Health Services Research Department Institute of Psychiatry De Crespigny Park London SE5 8AF UK Background Antipsychotic agents have been a mainstay in the manage- ment of schizophrenia since they were introduced in the 1950s (Moore 1999). Whilst effective in ameliorating many of the distressing symptoms of schizophrenia, they are associated with a range of problematic side-effects including extrapyramidal symptoms (EPS). Up to 75% of patients treated with conventional antipsychotics experi- ence EPS (Casey 1996), which are not only distressing but are a major cause of noncompliance (van Putten 1974). Despite the distress and increased risk of noncompliance associated with the side-effects of antipsychotic medica- tion, a number of studies have found that many side-effects go undetected by clinicians. In an examination of 55 CPNs’ practice in assessing side-effects, Bennett et al. (1995) reported that they asked patients about only three or four

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Journal of Psychiatric and Mental Health Nursing, 2001, 8, 191–196

© 2001 Blackwell Science Ltd 191

The use of outcome measures to evaluate the efficacy andtolerability of antipsychotic medication: a comparison of Thorngraduate and CPN practiceR. GRAY1 rn bsc(hons), T. WYKES2 phd , A.-M. PARR3, E. HAILS4 rn msc enb a48 pgce &

K. GOURNAY5 cbe mphil phd cpsychol afbpss frcn rn1MRC Fellow, Health Services Research Department, Institute of Psychiatry, 2Professor of Rehabilitation andClinical Psychology, Department of Psychology, 3Research Worker, 4Thorn-Tutor, and 5Professor of PsychiatricNursing, Health Services Research Department, Institute of Psychiatry, De Crespigny Park, London, UK

GRAY R., WYKES T., PARR A.-M., HAILS E. & GOURNAY K. (2001) Journal of Psychiatric and Mental Health Nursing 8, 191–196

The use of outcome measures to evaluate the efficacy and tolerability of antipsychotic medication: a comparison of Thorn graduate and CPN practice

Assessing the tolerability and efficacy of treatment with antipsychotic medication is a vital

part of mental health care. Research has suggested that many side-effects go undetected by

clinicians and there is a need to use standardized assessment tools to ensure that treatments

are comprehensively evaluated. The training of Community Psychiatric Nurses (CPNs),

who provide much of patients’ care, should focus on enhancing skills in using such assess-

ments. This study aimed to examine differences in the use of standardized assessments of

antipsychotic side-effects and psychopathology by CPNs and Thorn graduates who had

received additional training in delivering psychosocial interventions. A questionnaire was

sent to 240 Thorn graduates and CPNs practising in England, with an overall adjusted

response rate of 54%. Thorn graduates reported using significantly more standardized

assessments of side-effects and psychopathology than CPNs. A trend in both groups

towards the use of measures that relied on patient self-report of side-effects was observed.

This study identified important deficiencies in current CPN practice. A programme of

targeted training may be a more realistic and efficient method of enhancing medication

management practices in large numbers of CPNs compared to the more expensive and time-

consuming Thorn programme.

Keywords: antipsychotic, CPN, survey, Thorn, training

Accepted for publication: 12 October 2000

Correspondence:

R. Gray

Health Services Research

Department

Institute of Psychiatry

De Crespigny Park

London

SE5 8AF

UK

Background

Antipsychotic agents have been a mainstay in the manage-

ment of schizophrenia since they were introduced in the

1950s (Moore 1999). Whilst effective in ameliorating

many of the distressing symptoms of schizophrenia, they

are associated with a range of problematic side-effects

including extrapyramidal symptoms (EPS). Up to 75% of

patients treated with conventional antipsychotics experi-

ence EPS (Casey 1996), which are not only distressing

but are a major cause of noncompliance (van Putten

1974).

Despite the distress and increased risk of noncompliance

associated with the side-effects of antipsychotic medica-

tion, a number of studies have found that many side-effects

go undetected by clinicians. In an examination of 55 CPNs’

practice in assessing side-effects, Bennett et al. (1995)

reported that they asked patients about only three or four

R. Gray et al.

192 © 2001 Blackwell Science Ltd, Journal of Psychiatric and Mental Health Nursing 8, 191–196

possible side-effects from antipsychotic medication. Similar

findings were reported by Gray (1998), who found that

fewer than 50% of the 27 CPNs surveyed routinely

assessed patients for EPS. However, even if CPNs do

perform an assessment of side-effects, a substantial

proportion of symptoms may still remain undetected.

Wieden et al. 1987) compared the assessment of EPS by

clinicians in routine practice with those of researchers

trained to use standardized assessments. The results

suggested that clinicians in routine practice only detected

26% of the patients with akathisia and 59% of the

patients with Parkinsonism that had been identified by the

researchers.

Perhaps these findings may be explained by clinicians

underestimating the importance of antipsychotic side-

effects. Evidence to support this conclusion comes from

Hoge et al. (1990), who prospectively interviewed 1434

patients admitted to four inpatient units during a six-

month period about refusal of treatment with anti-

psychotic medication. Thirty-five per cent of noncompliant

patients cited side-effects as the main reason for stopping

medication, whilst only 7% of clinicians gave the same

reason.

Evaluating the efficacy and tolerability of treatments

is clearly a critical component of good mental health

care. The use of valid and reliable measures, such as the

Liverpool University Neuroleptic Side-Effect Rating Scale

(LUNSERS; Day et al. 1995) has been recognized as the

most robust way of reviewing the impact of pharmaco-

logical interventions. Indeed, such practice is embedded

within the new National Service Framework for mental

health (DoH 1999).

Since 1992, a major post-registration training initiative

for CPNs has been the Thorn course, developed jointly by

Manchester University and the Institute of Psychiatry in

London (Lancashire et al. 1997). This skills-based pro-

gramme aims to train mental health professionals to use

evidenced-based psychosocial interventions (problem-

orientated case management, cognitive behavioural

interventions for psychosis and schizophrenia family

work), including the use of standardized assessments of

psychopathology and antipsychotic side-effects. Trainees

have approximately 250 hours’ contact with trainers of

which around 12 hours is devoted specifically to medica-

tion management (Lancashire et al. 1997, Gournay &

Birley 1998).

This study aimed to provide evidence of Thorn

graduates’ and CPNs’ reported use of recognized out-

come measures to evaluate the efficacy and tolerability of

antipsychotic medication. Differences in Thorn graduates’

and CPNs’ perceptions of their role in medication man-

agement, knowledge about psychopharmacology and

future training requirements were also explored.

Method

Power calculation

A power calculation was performed to determine the

number of CPNs which would need to be surveyed to

detect the proportion who utilize standardized anti-

psychotic side-effect scales in clinical practice. Assuming a

population of 6700 CPNs (Brooker & White 1997) and

that an estimated 40% use at least one recognized assess-

ment tool (Gray 1998), a sample of 91 CPNs would be

necessary to achieve a confidence level of 95%. Assuming

a non-response rate of 40–60%, a sample size of 240

was estimated to meet the requirements of the power

calculation.

Sample selection

As no comprehensive national database of CPNs working

in the UK exists, the sample for this study was generated

using two different methods. Thorn graduates were iden-

tified by contacting the course leaders in both London and

Manchester requesting a list of the names and addresses of

all trainees who had successfully completed training. CPNs

were identified by inviting six geographically diverse Trusts

throughout England where Thorn training was not cur-

rently provided to participate. Those Trusts who agreed to

take part provided a list of CPNs currently in clinical prac-

tice who met the following inclusion criteria: they were a

registered nurse, currently engaged in clinical practice, with

a caseload of patients living in a community setting. From

these lists of 227 CPNs and 246 Thorn graduates the

sample was selected. Each nurse was allocated a number,

which was then sorted into a random order. The first 120

nurses in each group (total 240) were then selected and sent

a brief questionnaire, with a covering explanatory letter

and consent form, to complete and return.

Questionnaire

The 38-item questionnaire was developed based on previ-

ous research (Bennett et al. 1995) and consultation with a

group of experienced clinicians and academics (a Professor

of Psychiatric Nursing, a Consultant Clinical Psychologist,

a Consultant Psychiatrist, a Clinical Nurse Specialist and

a Thorn Tutor). The questionnaire, which was intended to

be brief and easy to complete, was designed to elicit infor-

mation about clinician demographics, caseload composi-

Use of outcome measures

© 2001 Blackwell Science Ltd, Journal of Psychiatric and Mental Health Nursing 8, 191–196 193

tion, use of valid and reliable assessment tools, knowledge

about psychopharmacology and training requirements.

The majority of questions required tick-box responses.

Information about the composition of caseloads was

obtained by asking CPNs to calculate the proportion of

their patients who were suffering from different disorders.

Respondents were also asked to list all the assessment tools

they regularly used in their clinical practice. Knowledge

about psychopharmacology was determined by asking

respondents to give an agree, disagree, or unsure response

to nine statements about psychopharmacology. A score of

2 was given for a correct answer, 1 for unsure, and 0 for

an incorrect answer, producing a total score ranging from

0 to 18. The expert group paid considerable attention to

devising a list of questions that a CPN should ideally be

able to answer given appropriate training. This method of

examining knowledge has been used before and has been

shown to be, potentially, reliable and easy to administer

(Gamble et al. 1994). The complete questionnaire is avail-

able from the authors on request.

The questionnaire was piloted on a cohort of 58 CPNs

(Gray 1998) and the analysis of these responses allowed

the questionnaire to be further refined, by removing un-

necessary items and rephrasing certain questions.

Questionnaires were sent out in November 1998,

together with a covering letter explaining the nature and

purpose of the study. A reminder letter was sent eight

weeks later if CPNs had not responded. Respondents

were asked to sign and return a consent form with the

questionnaire.

Statistics

Data were analysed using SPSS for windows, version 8.0.

To identify between group differences, independent sample

t-tests were used. The chi-square statistic (c2) was utilized

to test for association. All tests were two-tailed.

Results

Response rates and non-response bias

Of the 240 questionnaires that were sent out 144 (60%)

were returned. Of these, 30 were excluded because respon-

dents either had never worked as CPNs or were not cur-

rently working as CPNs, giving an adjusted response rate

of 54%. All returned questionnaires contained completed

consent forms. There was no significant difference in the

adjusted response rate from Thorn graduates (53%) and

CPNs (54%). A response rate of 54% may represent a

significant non-response bias. However, given that 30

respondents (mainly Thorn graduates) were not currently

working as CPNs or had never worked as CPNs, it is

likely that the same was true of a proportion of the

non-responders, which may reduce the bias.

Demographics

The demographic profile of the two groups did not differ

significantly. Of the 114 respondents, 49% were male,

90% classified themselves as white and had a mean age of

40 years (range 24–57, SD 7.5). The majority of CPNs

(69%) and Thorn graduates (64%) were employed at

grade ‘G’. Both CPNs and Thorn graduates had, on

average, 15 years post-registration experience, and there

was no significant difference in time spent working in the

community (CPNs 8 years; Thorn graduates 7 years). All

Thorn graduates and 69% of CPNs were qualified to at

least undergraduate diploma level.

The role of the CPN

Although Thorn graduates had significantly smaller case-

loads than CPNs (24 vs. 37; t = 4.53, d.f. = 110, P <

0.0009), there was no significant difference in the propor-

tion of patients with serious and enduring mental disorders

(schizophrenia, dementia, bi-polar illness, severe eating

disorder; Goldberg & Gournay 1997).

Respondents were asked to indicate whether a range of

commonly used therapeutic approaches were an impor-

tant part of their role as a CPN. The list included the

following medication management interventions: assessing

patient’s mental state (to evaluate pharmacological inter-

ventions), monitoring antipsychotic side-effects and

enhancing compliance. The results are presented in Table

1. No significant difference between the two groups was

observed, with both indicating that medication manage-

ment interventions are an important part of their role.

Assessing side-effects

There was no significant difference in the frequency with

which Thorn graduates and CPNs reported asking patients

about antipsychotic side-effects, with 80% of both groups

assessing side-effects at least once a month. However, side-

effect assessment tools were used by significantly more

Thorn graduates than CPNs (62% vs. 25%; c2 = 8.61, d.f.

= 1, P = 0.003). The most widely used measure of anti-

psychotic side-effects, in both groups, was the LUNSERS

(Liverpool University Neuroleptic Side-Effect Rating Scale;

Day et al. 1995), although this was used by significantly

more Thorn graduates than CPNs (56% vs. 25%; c2 =

R. Gray et al.

194 © 2001 Blackwell Science Ltd, Journal of Psychiatric and Mental Health Nursing 8, 191–196

11.38, d.f. = 1, P = 0.001). The Simpson Angus Extrapyra-

midal Side-Effect Rating Scale (Simpson & Angus 1970)

was also used by a small number of Thorn graduates,

which was significantly greater than the number of CPNs

using it (10% vs. 0%; c2 = 6.69, d.f. = 1, P = 0.01). Fewer

than 5% of both Thorn graduates and CPNs reported

using the AIMS (Abnormal Involuntary Movement Scale;

Guy 1976). The use of self-developed measures to assess

side-effects was also reported by significantly more Thorn

graduates (24% vs. 5%, c2 = 9.16, d.f. = 1, P = 0.002). No

other measures were reported as being used.

Assessment of psychopathology

The only recognized assessment of psychopathology used

by respondents in either group was the KGV (Krawiecka

et al. 1977). Thorn graduates were significantly more likely

to report using it in clinical practice than CPNs (40% v

5%, c2 = 21.73, d.f. = 1, P < 0.0009).

Knowledge about psychopharmacology

No significant difference in mean total scores on the

knowledge questionnaire were observed between Thorn

graduates (mean 14.64; range 8–18; s.d. 1.92) and CPNs

(mean 13.58; range 9–17; s.d. 1.85). Scores were at the

upper end of the 0–18 range and may indicate that res-

pondents generally had good levels of knowledge about

psychopharmacology. There were consistent deficits in

both groups’ understanding about novel antipsychotic

treatments and the causes and management of EPS.

Need for training

Respondents were asked to rate their individual training

needs on a 1 (low priority) to 9 (high priority) scale and

results are shown in Table 2. Generally, respondents

reported a need for training in all proposed areas with the

exception of anxiety management and relaxation. Both

groups rated medication management interventions, risk

assessment and suicide prevention as high priorities for

training. Thorn graduates placed a significantly greater

emphasis on the need for training in compliance and

cognitive behavioural interventions.

Discussion

The aim of this study was to establish whether CPNs and

Thorn graduates differ in their reported use of recognized

outcome measures to evaluate pharmacological inter-

ventions. Results demonstrate that Thorn graduates report

using more standardized side-effect and mental state

assessment tools than do CPNs but were no more knowl-

edgeable about psychopharmacology. The sample meets

the requirements of the power calculation and the profile

of respondents is comparable to the national survey of

CPN services (Brooker & White 1997), suggesting that

results may be generalized.

The majority of CPNs indicated that evaluating the

effects of antipsychotic medication was part of their role.

However, despite evidence from Wieden et al. (1987) that

clinicians fail to detect a substantial proportion of side-

effects if they do not use assessment tools, only a minority

Table 1The role of the CPN

percentage of respondentswho agreed that intervention was an important part of their role

Intervention CPN Thorn

Assessing mental state 96.9 100.0Risk assessment 90.6 95.8Monitoring side-effects 87.3 95.8Suicide prevention 87.3 91.7Crisis intervention 71.9 85.7Case management 65.6 77.6Enhancing compliance 61.9 75.5Mental health promotion 58.7 58.0Giving depots 50.0 60.4Anxiety management 40.6 44.7Cognitive behaviour therapy* 31.3 65.3Counselling 30.6 25.0Family work† 27.0 61.2Relaxation therapy 18.0 20.8

* = 13.98, d.f. = 2, P = 0.001.† = 15.46, d.f. = 2, P < 0.0009.

Table 2Priorities for training (1 low priority – 9 high priority)

Priority for training score

Training area CPN Thorn

Suicide prevention 8.40 8.38Risk assessment 8.35 8.47Assessing mental state 8.28 8.44Monitoring side-effects 7.87 8.36Crisis intervention 7.49 7.88Care programme approach 7.37 7.42Case management 7.29 7.77Mental health promotion 7.23 7.55Enhancing compliance* 6.77 7.58Cognitive behaviour therapy† 6.57 7.78Family work‡ 6.48 8.02Giving depots 6.24 6.61Counselling§ 6.07 5.14Relaxation therapy 5.18 5.63Anxiety management 5.60 6.06

*t = 107, P = 0.010.†t = 108, P < 0.0009.‡t = 109, P < 0.0009.§t = 2.3, P = 0.022.

Use of outcome measures

© 2001 Blackwell Science Ltd, Journal of Psychiatric and Mental Health Nursing 8, 191–196 195

of CPNs reported that they made use of such procedures

in their practice. This suggests that respondents are failing

to evaluate how well their patients are tolerating antipsy-

chotic medication, a finding that is consistent with Bennett

et al. (1995) and Gray (1998). That only a small number

of CPNs reported using measures of psychopathology also

appears to indicate that a regular review of the efficacy of

medication is not being performed. The failure of CPNs to

evaluate both the tolerability and efficacy of medication is

incongruent with the standards set out in the National

Service Framework (DoH 1999) and may expose a lack of

training in the use of assessment tools. The high priority

respondents, particularly Thorn graduates, placed on

medication management training may indicate an aware-

ness of the deficits in their current practice.

Respondents in both groups used primarily self-report

scales such as the LUNSERS to detect side-effects. Whilst

self-report is useful, it relies on patients being aware of

side-effects. This is not always the case; for example

patients may not always be aware of tremor, stiffness or

abnormal body movements. This highlights the importance

of other types of assessment tools that use observation and

physical examination as a basis for rating.

Although the results from the knowledge component

of the questionnaire should be treated with caution, no

significant between-group differences in knowledge about

psychopharmacology were found. However, important

deficits in knowledge were observed among both groups,

particularly about atypical antipsychotics. This may reflect

the comparatively small amount of time within the Thorn

programme devoted specifically to psychopharmacology. It

is possible that a poor understanding about psychophar-

macology may limit the strategies used by both groups to

help patients manage antipsychotic side-effects. Perhaps

there is a need to increase the amount of time dedicated to

psychopharmacology within Thorn training.

Results from this study suggest that Thorn graduates

make more use of outcome measures to evaluate the

efficacy and tolerability of antipsychotic medication and

suggest that training has been beneficial in this area.

However, only about half stated that they were currently

using such measures in their clinical practice. This finding

suggests that factors other than training, such as caseload

size and lack of clinical supervision, may also have an

important influence on practice.

Conclusion

The evaluation of both the efficacy and tolerability of

antipsychotic treatment is critical if side-effects are to be

minimized and compliance enhanced. The results of this

study confirm previous research and suggest that only a

minority of CPNs use standardized measures to evaluate

pharmacological interventions. Although Thorn graduates

report using more outcome measures in routine clinical

practice, they tend to rely on self-report checklists to iden-

tify side-effects. Around a third indicated that they no

longer used the measures they had been trained in; the

reasons for this are unclear. The study also highlights

important deficiencies in both groups’ understanding of

psychopharmacology. As a model for increasing the use of

outcome measures to evaluate antipsychotic medication,

Thorn training may be useful. However, many patients

continue to experience unwanted side-effects that could

easily be treated if CPNs detected them. Thorn training is

relatively time-consuming and consequently it will not be

possible to train all of the 6700 CPNs currently in prac-

tice. An alternative model is needed to achieve widespread

changes in practice rapidly and cost-effectively. A brief

manualized medication management training package,

which can be disseminated to entire community mental

health teams, may be a more realistic and effective method

of enhancing practice in this area. Perhaps only when

CPNs receive the training they require will the standards

defined in the National Service Framework (DoH 1999) be

achieved.

References

Bennett J., Done J. & Hunt B. (1995) Assessing the side effects

of antipsychotic drugs: a survey of CPN practice. Journal ofPsychiatric and Mental Health Nursing 2, 177–182.

Brooker C. & White E. (1997) The Fourth QuinquennialNational Community Mental Health Nursing Census ofEngland and Wales. University of Manchester, Manchester.

Casey D. (1996) Extrapyramidal syndromes: epidemiology,

pathophysiology and the diagnostic dilemma. CNS Drugs 5,

1–12.

Day J.C., Wood G., Dewey M. & Bentall R.P. (1995) A self-rating

scale for measuring neuroleptic side-effects: validation in a

group of schizophrenic patients. British Journal of Psychiatry166, 650–653.

DoH (1999). The National Service Framework for Mental Health.Department of Health, London.

Gamble C., Midence K. & Leff J. (1994) The effect of family work

training on mental health nurses’ attitude to and knowledge

of schizophrenia. Journal of Advanced Nursing 19, 893–

896.

Goldberg D. & Gournay K. (1997) The General Practitioner, thePsychiatrist and the Burden of Mental Health Care. Maudsley

Discussion Paper No. 1. Institute of Psychiatry, London.

Gournay K. & Birley J. (1998) Thorn: a new approach to mental

health training. Nursing Times 94, 54–55.

Gray R. (1998) Primary care of schizophrenia: what are the roles

of practice and community psychiatric nurses. CommunityMental Health 1, 5–7.

Guy W. (1976) Assessment Manual for Psychopharmacology.Department of Education and Welfare, Washington DC.

R. Gray et al.

196 © 2001 Blackwell Science Ltd, Journal of Psychiatric and Mental Health Nursing 8, 191–196

Hoge S., Appelbaum P., Lawlor T. et al. (1990) A prospective,

multicentre study of patients’ refusal of antipsychotic medica-

tion. Archives of General Psychiatry 47, 949–956.

Krawiecka M., Goldberg D. & Vaughn M. (1977) A standardised

psychiatric assessment scale for chronic psychiatric patients.

Acta Psychiatrica Scandinavica 55, 299–308.

Lancashire S., Haddock G., Tarrier N. et al. (1997) The impact

of training community psychiatric nurses to use psychosocial

interventions with people who have severe mental health prob-

lems. Psychiatric Services 48, 39–41.

Moore N.A. (1999) Behavioural pharmacology of the new gen-

eration of antipsychotic agents. British Journal of Psychiatry174, 5–11.

van Putten T. (1974) Why do schizophrenic patients refuse to

take their medication. Archives of General Psychiatry 31,

67–72.

Simpson G.M. & Angus J.W.S. (1970) Drug induced extrapyra-

midal disorders. Acta Psychiatrica Scandinivica 45, 11–19.

Wieden P.J., Shaw E. & Mann J. (1987) Causes of neuroleptic

non-compliance. Psychiatric Annals 16, 571–578.